Potential mediators of the acute-phase plasma glycoprotein response to inflammation were studied in primary suspension cultures of rat hepatocytes in vitro. 3H-Leucine incorporation into haptoglobin was compared with that of albumin as a measure of the synthesis of an acute-phase glycoprotein relative to that of a protein not participating in the acute-phase plasma protein response. The addition of hydrocortisone or a hormone mixture containing hydrocortisone, glucagon, triiodothyronine, and somatotropin to the hepatocyte suspensions produced a differential stimulation of haptoglobin synthesis. Among factors demonstrating no effect on the relative synthesis of haptoglobin in vitro are insulin, endotoxin, prostaglandins E1, E2, A1, A2 and F2 alpha and asialo- and asialo-, aglacto- preparations of haptoglobin and orosomucoid. Currently under investigation as other potential mediators are complement components and pyrogenic products from stimulated leukocytes.